Peripheral Blood of Coronavirus Survivors to Identify Virus-Neutralizing Antibodies
The diversity of the antibody repertoire is generated by somatic recombination of immunoglobulin gene segments during early B cell development in the bone marrow. This random rearrangement process and the following antibody-maturation process generate a diverse repertoire of antibodies including antibodies that recognize pathogens (e.g. Coronaviruses in Coronavirus-infected individuals). In order to study the B cell repertoire of individuals who have been exposed to the Coronaviruses (a group of pathogenic viruses that includes Wuhan Coronavirus (nCoV-2019 recently renamed SARS-CoV-2 responsible for COVID-19 severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) we developed a method to clone and express antibodies from single human B cells at different stages of development or B cells that are specific for defined antigens (e.g. Coronavirus-spike proteins). Our goal with this study is to identify antibodies that target and potentially neutralize the Coronaviruses in individuals that have been exposed to the virus and have cleared the infection. We have previously shown that antibodies with potent neutralizing activity can be identified in HIV-infected and ZIKA-convalescent subjects. These antibodies can protect non-human primates from infection and are therefore highly valuable for HIV and ZIKA-vaccine design. Moreover we have shown that broadly neutralizing anti-HIV antibodies are able to suppress viral replication in HIV-infected humanized mice and non-human primates. As a result of these findings some of these antibodies are currently tested in clinical trials. Therefore we have a broad knowledge about anti-viral neutralizing antibodies. We want to apply this knowledge to identify Coronavirus-neutralizing antibodies that might be of potential benefit to protect and treat Coronavirus infection. In order to identify antigen-specific B lymphocytes single B cells will be isolated by fluorescence activated single cell sorting (FACS). Immunoglobulin heavy and light chain rearrangements will be cloned from purified individual cells and expressed in vitro to produce recombinant antibodies for further reactivity testing. Identified Coronavirus reactive antibodies will be further tested for Coronavirus-neutralization using in vitro assays and in vivo models but this will be performed by virologists elsewhere. This work will provide a valuable insight into specific B cell response against Coronavirus-infection. B cells and other cells of the immune system that will be analyzed will be obtained from a leukapheresis procedure or from a regular blood draw.
- Eligible Ages
- Between 18 and 75
- Eligible Genders
- Accepts Healthy Volunteers
- Male or Female 18-75 years of age.
- Individuals who were infected with the Coronavirus but have been free of symptoms of the Coronavirus for at least 14 days and are medically stable and not on mandatory isolation or quarantine.
- Individuals who are close contacts with someone who tested positive for the Coronavirus and have been asymptomatic for at least 14 days from the exposure.
- In the opinion of the Principal Investigator or designee the subject has the ability to understand the information contained in the informed consent form and can provide written consent.
- Individuals exposed to the Coronavirus and with symptoms of active disease.
- Individuals who are not medically stable.
- Individuals infected or exposed to the Coronavirus and under mandatory isolation or quarantine as defined by the Department of Health.
- Study Type
- Rockefeller University
Study ContactRecruitment Office